RESUMO
Cytophilic (cell-adhesive) materials are very important for tissue engineering and regenerative medicine. However, for engineering hierarchically organized tissue structures comprising different cell types, cell-specific attachment and guidance are decisive. In this context, materials made of recombinant spider silk proteins are promising scaffolds, since they exhibit high biocompatibility, biodegradability, and the underlying proteins can be genetically functionalized. Here, previously established spider silk variants based on the engineered Araneus diadematus fibroin 4 (eADF4(C16)) are genetically modified with cell adhesive peptide sequences from extracellular matrix proteins, including IKVAV, YIGSR, QHREDGS, and KGD. Interestingly, eADF4(C16)-KGD as one of 18 tested variants is cell-selective for C2C12 mouse myoblasts, one out of 11 tested cell lines. Co-culturing with B50 rat neuronal cells confirms the cell-specificity of eADF4(C16)-KGD material surfaces for C2C12 mouse myoblast adhesion.
Assuntos
Fibroínas , Aranhas , Animais , Camundongos , Ratos , Seda/química , Proteínas de Artrópodes/química , Proteínas de Artrópodes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Fibroínas/química , Peptídeos , Aranhas/metabolismoRESUMO
In the human body, cells in a tissue are exposed to signals derived from their specific extracellular matrix (ECM), such as architectural structure, mechanical properties, and chemical composition (proteins, growth factors). Research on biomaterials in tissue engineering and regenerative medicine aims to recreate such stimuli using engineered materials to induce a specific response of cells at the interface. Although traditional biomaterials design has been mostly limited to varying individual signals, increasing interest has arisen on combining several features in recent years to improve the mimicry of extracellular matrix properties. Tremendous progress in combinatorial surface modification exploiting, for example, topographical features or variations in mechanics combined with biochemical cues has enabled the identification of their key regulatory characteristics on various cell fate decisions. Gradients especially facilitated such research by enabling the investigation of combined continuous changes of different signals. Despite unravelling important synergies for cellular responses, challenges arise in terms of fabrication and characterization of multifunctional engineered materials. This review summarizes recent work on combinatorial surface modifications that aim to control biological responses. Modification and characterization methods for enhanced control over multifunctional material properties are highlighted and discussed. Thereby, this review deepens the understanding and knowledge of biomimetic combinatorial material modification, their challenges but especially their potential.